3,4-dihydro-2H-pyran → 5-bromo-N-methoxy-N-methyl-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-b]pyridine-3-carboxamide

HRID 589440Notes

Reaction equation

HRID 589440 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C:10]([C:11]([N:13]([O:15][CH3:16])[CH3:14])=[O:12])=[N:9][NH:8][C:5]2=[N:6][CH:7]=1.[O:17]1[CH:22]=[CH:21][CH2:20][CH2:19][CH2:18]1.CC1C=CC(S([O-])(=O)=O)=CC=1.C1C=C[NH+]=CC=1>C(Cl)Cl>[Br:1][C:2]1[CH:3]=[C:4]2[C:10]([C:11]([N:13]([O:15][CH3:16])[CH3:14])=[O:12])=[N:9][N:8]([CH:18]3[CH2:19][CH2:20][CH2:21][CH2:22][O:17]3)[C:5]2=[N:6][CH:7]=1

Participants

5

Reactant 3

HCID 80803,4-dihydro-2H-pyran2×HCID 466102Benzenesulfonic acid, 4-methyl-, compd. with pyridine (1:1)2×HCID 178502688HCID 178502688, compound

Product 1

HCID 583780195-bromo-N-methoxy-N-methyl-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-b]pyridine-3-carboxamideYield 93.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 5-bromo-N-methoxy-N-methyl-1H-pyrazolo[3,4-b]pyridine-3-carboxamide (XIX) (0.250 g, 0.88 mmol) in dry DCM (10 mL) was added 3,4-dihydro-2H-pyran (0.179 mL, 1.98 mmol) and PPTS (22 mg, 0.08 mmol) and refluxed 5 h under nitrogen. Another equivalent of 3,4-dihydro-2H-pyran (0.179 mL, 1.98 mmol) and PPTS (22 mg, 0.08 mmol) was added and the solution was further heated at refluxed overnight under nitrogen. The solution was cooled, diluted with DCM, washed subsequently with a saturated aqueous NaHCO3 solution and brine. The organic layer was dried over MgSO4, filtered and concentrated under reduced pressure to give 5-bromo-N-methoxy-N-methyl-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-b]pyridine-3-carboxamide (XX) as a viscous liquid (302 mg, 0.82 mmol, 93% yield). 1H NMR (CDCl3) δ ppm 1.51-1.62 (m, 2H), 1.91-2.13 (m, 2H), 2.33-2.44 (m, 2H), 3.40 (s, 3H), 3.66 (m, 1H), 3.75 (s, 3H), 3.87-3.98 (m, 1H), 6.07 (dd, J=10.07 Hz, J=2.52 Hz, 1H), 8.57 (d, J=3.01 Hz, 1H), 8.73 (d, J=3.01 Hz, 1H); ESIMS found for C14H17BrN4O3 m/z 369.4 (M+H).

Workup

  1. temperaturerefluxed 5 h under nitrogen
  2. temperaturethe solution was further heated
  3. temperatureat refluxed overnight under nitrogen
  4. temperatureThe solution was cooled
  5. washwashed subsequently with a saturated aqueous NaHCO3 solution and brine
  6. dry with materialThe organic layer was dried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-ef4b055693e540c5bf4cd3403e38089b
Source dataset
uspto-grants-2016_01
Patent number
US09233104B2

Reaction notes

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